Zhongqi Shen

Molecular design, synthesis, and structure–Activity relationships leading to the potent and selective p56lck inhibitor BMS-243117

A series of structurally novel benzothiazole based small molecule inhibitors of p56(lck) were prepared to elucidate their structure-activity relationships (SARs), selectivity and cell activity in the T-cell proliferation assay. BMS-243117 (compound 2) is identified as a potent, and selective Lck inhibitor with good cellular activity (IC(50)=1.1 microM) against T-cell proliferation.

Rapid synthesis of triazine inhibitors of inosine monophosphate dehydrogenase

A series of novel triazine-based small molecule inhibitors (IV) of inosine monophosphate dehydrogenase was prepared. The synthesis and the structure-activity relationships (SAR) derived from in vitro studies are described.

Inhibitors of inosine monophosphate dehydrogenase: SARs about the N-[3-Methoxy-4-(5-oxazolyl)phenyl moiety

The first reported structure-activity relationships (SARs) about the N-[3-methoxy-4-(5-oxazolyl)phenyl moiety for a series of recently disclosed inosine monophosphate dehydrogenase (IMPDH) inhibitors are described. The syntheses and in vitro inhibitory values for IMPDH II, and T-cell proliferation (for select analogues) are given.

Discovery and initial SAR of imidazoquinoxalines as inhibitors of the Src-family kinase p56Lck

We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck with excellent potency (IC50s<5 nM) as well as good cellular activity against T-cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the requirement for the core heterocycle in addition to an optimal 2,6-disubstituted aniline group.

3-Cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure–Activity relationships

A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.

Novel diamide-based inhibitors of IMPDH

A series of novel amide-based small molecule inhibitors of inosine monophosphate dehydrogenase is described. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are presented.

The TosMIC approach to 3-(Oxazol-5-yl) indoles: application to the synthesis of indole-based IMPDH inhibitors

A modified approach to the synthesis of 3-(oxazolyl-5-yl) indoles is reported. This method was applied to the synthesis of series of novel indole based inhibitors of inosine monophosphate dehydrogenase (IMPDH). The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for this new series of inhibitors is given.

Quinolone-Based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues

The synthesis and the structure-activity relationships (SAR) of analogues derived from the introduction of basic residues on ring D of quinolone-based inhibitors of IMPDH are described. This led to the identification of compound 27 as a potent inhibitor of IMPDH with significantly improved aqueous solubility over the lead compound 1.

Novel inhibitors of IMPDH

A series of novel quinolone-based small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH) was explored. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are described.